Small mitochondrial protein NERCLIN regulates cardiolipin homeostasis and mitochondrial ultrastructure.

Cardiolipin (CL) is an essential phospholipid for mitochondrial structure and function. Here, we present a small mitochondrial protein, NERCLIN, as a negative regulator of CL homeostasis and mitochondrial ultrastructure. Primate-specific NERCLIN is expressed ubiquitously from the GRPEL2 locus on a tightly regulated low level. NERCLIN overexpression severely disrupts mitochondrial cristae structure and induces mitochondrial fragmentation. Proximity labeling and immunoprecipitation analysis suggested interactions of NERCLIN with CL synthesis and prohibitin complexes on the matrix side of the inner mitochondrial membrane. Lipid analysis indicated that NERCLIN regulates mitochondrial CL content. Furthermore, NERCLIN is responsive to heat stress ensuring OPA1 processing and cell survival. Thus, we propose that NERCLIN contributes to the stress-induced adaptation of mitochondrial dynamics. Our findings add NERCLIN to the group of recently identified small mitochondrial proteins with important regulatory functions.

Unveiling the mechanisms and challenges of cancer drug resistance.

Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer treatment strategies are evolving due to innate and acquired resistance capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells to survive and progress under unfavorable conditions. Although the mechanism of drug resistance is being widely studied to generate new target-based drugs with better potency than existing ones. However, due to the broader flexibility in acquired drug resistance, advanced therapeutic options with better efficacy need to be explored. Combination therapy is an alternative with a better success rate though the risk of amplified side effects is commonplace. Moreover, recent groundbreaking precision immune therapy is one of the ways to overcome drug resistance and has revolutionized anticancer therapy to a greater extent with the only limitation of being individual-specific and needs further attention. This review will focus on the challenges and strategies opted by cancer cells to withstand the current therapies at the molecular level and also highlights the emerging therapeutic options -like immunological, and stem cell-based options that may prove to have better potential to challenge the existing problem of therapy resistance. Video Abstract.

The potential impact of renin-angiotensin system inhibitors on cancer survival and recurrence: A systemic review and meta-analysis.

Renin-angiotensin-system inhibitors (RASi), specifically angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), are widely used anti-hypertensives. Their impact on the prognostic outcomes among cancer patients has been subject to scrutiny and debate. The aim of this study is to evaluate the effect of RASi on survival in cancer patients. We systematically searched PubMed, Web of Science, Embase and Cochrane Library for relevant studies published until April 1st, 2022. All the studies, interventional or observational, which examined effects of ARBs and ACEi on cancer prognosis compared to a control group and reported the survival outcomes and Hazards Ratios were included in the analysis. From each study, pooled hazard ratios (HR) with corresponding 95% confidence intervals (95% CI) were identified and collected. Subgroup analysis was conducted to investigate heterogeneity. Sixty-one studies were included in this meta-analysis. Data of 343,283 participants were used in the study. It was found that RASi improved overall survival (OS) (HR=0.88; 95% CI: 0.82-0.93; P<0.0001), progression free survival (PFS) (HR=0.72; 95% CI: 0.65-0.79; P<0.00001), disease specific survival (DSS) (HR=0.86; 95% CI: 0.71-1.04; P=0.03), and recurrence free survival (RFS) (HR=0.74; 95% CI: 0.58-0.93; P=0.01) in cancer patients. The effect of RASi on OS varied depending on the type of cancer or type of RASi (ACEi or ARBs), according to subgroup analysis. The usage of RAS inhibitors has a positive impact on survival outcomes and recurrence among cancer patients.

Dual Fluorimetric Sensor for Tandem Detection of Cadmium and Cysteine: An Approach for Designing a Molecular Keypad Lock System.

A fluorimetric sensor for dual and sensitive detection of Cd2+ ion and Cysteine (based on 2-picolylamine platform) was developed.The sensor was designed and synthesized by simple condensation method and characterized by using common spectroscopic methods. The observations made from the kinetics of absorption and emission profile shows that probe Pdac behaves as ''ON-OFF'' fluorescent quenching sensor for cadmium ions. The probe exhibit selectivity in fluorescence quenching behaviour over other competitive metal ions, and also the Pdac-Cd2+ ensemble behave as an efficient ''OFF-ON'' type sensor for an essential amino acid Cysteine. Moreover, this dual sensing nature of the sensor makes it successfully applied for the designing of a molecular keypad lock system.

Band Gap Alteration of Halide Mixing in Hybrid Perovskites: A First-Principles Study with Statistical Analysis.

Despite numerous studies on the band gap of three-dimensional halide perovskites using the first-principles calculations, there are still significant discrepancies between theoretical and experimental values. Various solutions have been proposed, such as employing a system-specific hybrid functional with varying degrees of exact exchange and explicitly incorporating spin-orbit coupling effects. Our research involved a comprehensive investigation of three typical lead-containing three-dimensional perovskites MAPbI3, MAPbBr3, and MAPbCl3 (MA = CH3NH3). Through a statistical analysis comparing mean absolute error (MAE) with experimental results, we demonstrated that the nonlocal van der Waals (vdW) density functional corrections (i.e., optB86b) yielded the most approximate lattice parameters in comparison to experimental values. Furthermore, based on these lattice parameters, the HSE06 hybrid functional is the optimal estimation of the band gap among all the options. Moreover, we investigated three sets of mixed three-dimensional halide perovskites by varying the halide component. This exploration contributes to the identification of MAPb(Br0.333I0.667)3 and MAPb(Cl0.333I0.667)3 as exhibiting the smallest band gap of 1.315 (1.867) eV and 1.313 (1.885) eV for PBE (HSE06), respectively. These band gaps were determined using the HSE06 method with the optimized lattice by PBE considering the optB86b corrections. The approach employed in this work produced a band gap trend closely aligned with experimental observations, underscoring the importance of adopting a reliable and material-independent computational strategy when screening new halide perovskite materials for optoelectronic applications.

Safety and efficacy of Withania somnifera for anxiety and insomnia: Systematic review and meta-analysis.

OBJECTIVE: Despite the historical neurological use of Withania somnifera, limited evidence supports its efficacy for conditions like anxiety and insomnia. Given its known anti-stress properties, this review evaluated its safety and efficacy for anxiety and insomnia. METHODS: We searched Medline, Cochrane Library, and Google Scholar until August 2023 for randomized controlled trials (RCTs) comparing W. somnifera to placebo in patients with anxiety and/or insomnia. Outcome measures included changes in anxiety levels via the Hamilton Anxiety Scale (HAM-A), Sleep Onset Latency (SOL), Total Sleep Time (TST), Wake After Sleep Onset (WASO), Total Time in Bed (TIB), Sleep Efficiency (SE), and Pittsburgh Sleep Quality Index (PSQI) score. We utilized a random-effect model for pooling Mean Differences (MD) with a 95% Confidence Interval (CI). Heterogeneity was assessed through sensitivity and subgroup analysis, and the quality of RCTs was evaluated using the Cochrane revised risk of bias tool. RESULTS: Pooled results from five RCTs (n = 254) demonstrated that W. somnifera significantly reduced HAM-A scores (MD = -5.96; [95% CI -10.34, -1.59]; P = 0.008; I2 = 98%), as well as sleep parameters such as SOL, TST, PSQI, and SE, but not WASO and TIB. CONCLUSION: While W. somnifera extracts yielded promising results, further research with larger sample sizes is needed to confirm its effects on anxiety and insomnia.

The evaluation of bacterial-augmented floating treatment wetlands for concomitant removal of phenol and chromium from contaminated water.

Contamination of aquatic ecosystems with organic and inorganic contaminants is a global threat due to their hazardous effects on the environment and human health. Floating treatment wetland (FTW) technology is a cost-effective and sustainable alternative to existing treatment approaches. It consists of a buoyant mat in which wetland plants can grow and develop their roots in a suspended manner and can be implemented to treat stormwater, municipal wastewater, and industrial effluents. Here we explored the potential of bacterial-augmented FTWs for the concurrent remediation of phenol and hexavalent chromium (Cr6+) contaminated water and evaluated treated water toxicity using Triticum aestivum L. (wheat) as a test plant. The FTWs carrying Phragmites australis L. (common reed) were inoculated with a consortium of four bacterial strains (Burkholderia phytofirmans PsJN, Acinetobacter lwofii ACRH76, Pseudomonas aeruginosa PJRS20, Bacillus sp. PJRS25) and evaluated for their potential to simultaneously remove phenol and chromium (Cr) from contaminated water. Results revealed that the FTWs efficiently improved water quality by removing phenol (86%) and Cr (80%), with combined use of P. australis and bacterial consortium after 50 days. The phytotoxicity assay demonstrated that the germination of wheat seed (96%) was significantly higher where bacterial-augmented FTWs treated water was used compared to untreated water. This pilot-scale study highlights that the combined application of wetland plants and bacterial consortium in FTWs is a promising approach for concomitant abatement of phenol and Cr from contaminated water, especially for developing countries like Pakistan where the application of advanced and expensive technologies is limited.

This pilot-scale research provides new interventions and information required for establishing a large-scale remediation framework for the effective, sustainable and eco-friendly remediation of phenol and Cr co-contaminated aquatic ecosystems, using bacterial augmented floating wetlands technology (FTWs).

Emergency endovascular and percutaneous urological interventions: A pictorial review.

Emergency endovascular and percutaneous urological interventions encompass various diagnostic and therapeutic procedures to address various genitourinary conditions. These urological interventions are life-saving in addressing complications following biopsy, post-nephrectomy, post-transplant, and post-trauma. Compared to other surgical fields, there are relatively fewer urological emergencies. However, they require prompt radiological diagnosis and urgent interventions. This pictorial essay emphasizes various urological emergencies and urgent interventional management.

Formulation and Evaluation of Meloxicam Hybrid nano Particles.

The goal of the present study was to prepare meloxicam (MX) entrapped hybrid particles (HPs) to enhance intestinal permeation and anti-inflammatory activity. MX-HPs were prepared by nanoprecipitation method using lipid, chitosan, poloxamer, and TPGS. The formulations (MX-HPs1, MX-HPs2, MX-HPs3) were evaluated for particle size, entrapment efficiency, and drug release to select the optimized composition and further evaluated for permeation study, stability study, morphology, interaction study, and anti-inflammatory activity by carrageenan-induced rat paw edema test. The prepared MX-HPs showed nano sized particles (198.5 ± 3.7 to 223.8 ± 2.1 nm) and PDI (<0.3), zeta potential (16.5 ± 2.7 to 29.1 ± 3.6 mV), and high entrapment efficiency (75.1 ± 4.7 to 88.5 ± 3.9%). The surface morphology was assessed by transmission electron microscopy and showed non-aggregated particles. Infra-red (IR) spectroscopy of pure MX as well as formulation revealed no drug-polymer interaction and X-ray diffraction confirmed the conversion of crystalline MX into amorphous form. The release study data revealed prolonged MX release for 24 h. The selected optimized hybrid particles (MX-HPs2) revealed a 2.3-fold improved enhancement ratio than free MX. The storage stability and gastrointestinal stability data demonstrated a stable formulation in SIF as well as SGF. The anti-inflammatory activity showed better therapeutic action than pure MX dispersion. From the study, it can be concluded that the prepared MX-HPs may be a promising delivery system for MX in treating inflammatory disorders.

Bleeding Control in Advanced Gastric Cancer; Role of Radiotherapy.

Objectives: The aim of our study is to see the efficacy of palliative radiotherapy (RT) for bleeding control in patients with advanced gastric cancer (AGC). Materials and Methods: It is a retrospective review based on observations of 74 AGC patients with a median age of 60 years (range 50-82 years) who had active tumour bleeding and were treated with palliative RT. Treatment response was assessed by both subjective symptom relief and objective change in parameters. Objective response to RT was defined by an increase in the median haemoglobin (Hb) level of patients and a decrease in number of packed red blood cell (RBC) units needed by patients after RT. Results: Response to haemostatic RT was observed in 52 patients out of 74 patients (70.27%). We observed a significant increase in mean Hb level after palliative RT. Pre-RT mean Hb was 6.14 ± 1.01 and post-RT mean Hb was 7.19 ± 1.75 (P < 0.05). Response to RT was also evident in a significant decrease in the number of packed RBC units post-haemostatic RT. The mean number of pre-RT transfused packed RBC units was 8.28 ± 3.76 and post-RT, it was 4.34 ± 2.91 (P < 0.05). The median overall survival was 90 days and the median transfusion-free survival was 40 days. Conclusion: RT may be an effective treatment option for bleeding control in AGC. In our study, we observed fair and reasonably durable haemostasis. A success rate of 70.24% was documented with clinical palliation, a higher Hb level and fewer transfusions after RT. This modality for bleeding control is more important and reliable in situations where alternative modalities are not feasible.

Evaluating the safety and efficacy of daprodustat for anemia of chronic kidney disease: a meta-analysis of randomized clinical trials.

PURPOSE: Anemia of chronic kidney disease (CKD) has traditionally been treated with recombinant human erythropoietin (rhEPO). Recently, daprodustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, has also been shown to increase hematocrit. It remains unclear whether daprodustat or rhEPO should be the treatment of choice for anemia of CKD. We aimed to assess the efficacy and cardiovascular safety of daprodustat versus rhEPO in CKD patients. METHODS: Online databases were queried in April 2022 for articles comparing the efficacy and safety of daprodustat in DD-CKD and NDD-CKD subgroups. Results from trials were pooled using a random-effects model. RESULTS: Data on 8245 CKD patients from eight clinical trials were included. Our results show that in comparison to rhEPO, daprodustat maintained the same efficacy in increasing hemoglobin levels in both the DD-CKD (MD: 0.10; 95% CI [- 0.13,0.34]; p = 0.50) and NDD-CKD (MD: - 0.01; 95% CI [- 0.38,0.35]; p = 0.95) subgroups. Daprodustat significantly lowered hepcidin levels and significantly increased TIBC in both subgroups. Additionally, daprodustat significantly reduced the incidence of major adverse cardiovascular events (MACE) (RR: 0.89; 95% CI: 0.89-0.98; p = 0.02) and its myocardial infarction (MI) component (RR: 0.74; 95% CI: 0.59-0.92; p = 0.006) in the DD-CKD subgroup. CONCLUSION: Daprodustat has similar efficacy compared to rhEPO for the treatment of anemia of CKD. On treatment, the reduced experience of MACE was reported in DD-CKD patients as compared to rhEPO. Furthermore, effects on iron metabolism varied by parameter, with daprodustat being superior to rhEPO in some cases and inferior in others.

Urease inhibition and DPPH radical scavenging potential of phytoconstituent from Alstonia scholaris and molecular docking interactions of bioactive luteolin with target proteins.

A polyphenolic flavone Luteolin (3',4',5,7-tetrahydroxyflavone) is found in various plants and is traditionally used in Chinese medicine. It is obtained from Alstonia scholaris (L.) R.Br Flower belonging to the family Apocynaceae while investigation. Various studies have been demonstrated the antioxidant or antiulcer potential of luteolin from different plant sources. In the present investigation the antioxidant or antiulcer effect of the Luteolin has been carried out using molecular docking simulations. The objective of this study was to analyze the antioxidant and antiulcer potential of luteolin obtained during isolation. The in vitro biological evaluation has been supported by the in silico studies using Autodock vina 4 shows the ligand-protein interaction of lute olin with 1HD2, 4GY7 and 3O1Q. Luteolin showed significant DPPH scavenging and urease inhibition activity i.e., 23.4 ± 0.87, 6.21±0.45 IC50 (uM) respectively as compared to the standard BHA and thiourea 44.2±0.45, 22.4±0.29 IC50 (uM) respectively. The docking simulations showed significant binding pocket sites with the respective proteins1HD2, 4GY7 and 3O1Q with the least binding energy -6.8, -8.0 and -8.2 kcal/mol respectively. Thus, Strong evidence has been presented with their confirmation structural interaction via molecular docking with proteins that serve as binding sites for available Luteolin molecule. The findings justify the application of the compound as a novel antioxidant and antiulcer agent.

Geraniol exerts its antiproliferative action by modulating molecular targets in lung and skin carcinoma cells.

Geraniol, an acyclic monoterpene present in several plant species' essential oils, is utilized as a food additive. It possesses potent antiproliferative and antitumor effects ascribed to its antiinflammatory, and antioxidant properties. The study aimed to understand geraniol's mechanism in human lung and skin cancer cells by employing molecular and cell target-based assays. SRB, NRU, MTT assays, qRT-PCR, molecular docking, and EAC model were used. Geraniol inhibits the proliferation of PC-3, A431, and A549 cells (~50%) and suppresses the activity of ornithine decarboxylase (15.42 ± 0.61 µM) and hyaluronidase (57.61 ± 8.53 µM) in A549 cells; LOX-5 (25.44 ± 3.50 µM) and hyaluronidase (90.71 ± 2.38 µM) in A431 cells. The qRT-expression analysis of the targeted gene depicts non-significant change at the transcriptional level of LOX-5 in A431 cells. A robust binding interaction of geraniol with molecular targets was observed in the molecular docking studies. In Ehrlich Ascites Carcinoma model, geraniol inhibit tumor growth by 50.08% at 75 mg/kg bw and was found to be safe up to 1,000 mg/kg bw in a toxicity study. Geraniol has two prenyl units allied head-to-tail and functionalized with one hydroxyl group at its tail end could be responsible for the antiproliferative activity. These observations provide evidence for geraniol to be used as a new prototype to develop a novel anticancer agent.

Anti-inflammatory and histopathological studies of leaves extracts of Croton bonplandianus in Albino rats.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used for the treatment and prevention of inflammation with the increase in number of side effects. Traditional plants have been used to treat inflammation owing to lesser adverse responses. Croton bonplandianus being an anti-inflammatory plant is extensively utilized all over the world. The methanolic and aqueous leaves extracts of Croton bonplandianus were exposed to anti-inflammatory activity in the carrageenan induced paw edema against standard diclofenac sodium, followed by the histopathlogical examination. The highest dose of methanolic extract were shown significant anti-inflammatory action having a significant P-value (P<0.05-0.001) compared with the diclofenac sodium (P<0.01-0.001) and aqueous extracts (P<0.5-0.01). The histopathological examination illustrated the vasodialation with reduction in the intensity of edema, neutrophils infiltration and other inflammatory cells. C. bonplandianus being a reactive oxygen species scavenger, responsible to exert an excellent anti-inflammatory activity. The present study confirmed the anti-inflammatory potential of drug extracts and authors recommended its utilization in the treatment of pain, inflammation and relevant diseases in future. However, phytochemical screening is to be required for the complete evaluation of active chemical constituent (s).

Authentication of various commercially available crude drugs using different quality control testing parameters.

The object of this study is to investigate the quality of various plant materials used in the preparation of herbal formulations using different methods of standardization to confirm their purity, safety and efficacy. However, it is uncertain whether these raw materials comply with the standards prescribed in the pharmacopeias. In the present study six raw materials' i.e. Foeniculum vulgarae, Curcuma longa, Aloe barbadensis, Plantago ovata, Zingiber officinale and Glycyrrhiza glabra have been obtained from the market and various quality control tests including microscopic evaluation, physico-chemical characteristics, thin layer chromatography (TLC), spectrophotometric assay (British Pharmacopoeia) and Fourier transform infrared spectroscopy (FTIR) have been performed to determine their compliance with the standards. The TLC has been used for the identification of the active ingredients on comparison of their Rf values with the reference standard. FTIR Spectra of these materials have been obtained to assign the functional groups present in the components of a particular material. Although these findings provide a significant data to herbal drug manufacturers for authentication of commercially available plant materials used in various herbal formulation.

The novel effect of propranolol in glibenclamide induced hepatotoxicity.

Glibenclamide (GBC) has been associated with hepatotoxicity in humans. This study conducted on rabbits to evaluate the hepatotoxicity of GBC alone and in combination therapy with propranolol (PPL). Liver enzymes like alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyltransferase (γ-GT) and bilirubin (BRB) are used to evaluate hepatotoxicity associated with GBC. Histological findings, micrometry and scanning electron microscopy (SEM) used to find hepatotoxicity by GBC and with PPL. GBC caused significant elevation of liver functions as compared to control (p<0.005). PPL reduced the level of serum ALT, ALP, γGT and BRB when administered with GBC (p<0.005). The results prevailed that there is a significant change in hepatic cells structure and significant change in its diameter of nucleus (p<0.05). The necrosis and granuloma with decreased in number of hepatic cells were observed in GBC treated rabbits. However, the combination of GBC with PPL has shown healthy and nearly similar structure as that of controlled group and confirmed by SEM microscopy. PPL reduced the blood flow to hepatic portal system and thus, avoid the noxious substances to liver. It is affirmed that the use of PPL offered beneficial effect on hepatotoxic drugs.

Gender Differences in Leadership Positions Among Academic Nuclear Medicine Specialists in Canada and the United States.

OBJECTIVE: Despite equal representation of genders among medical students, women continue to be underrepresented in the field of academic diagnostic radiology. These differences are manifest across subspecialties in academic medicine and even in diagnostic radiology. There are limited data available addressing diversity among nuclear medicine specialists. Thus, our primary objective was to compare gender representation in academic and leadership positions among faculty members in nuclear medicine in Canada and the United States. Our secondary objective was to study the influences to account for the existing disparity in academic nuclear medicine. MATERIALS AND METHODS: Using the Fellowship and Residency Electronic Interactive Database (FREIDA) and Canadian Resident Matching Service (CaRMS), we created a database of faculty members in nuclear medicine. For assessment of academic performance, the h-index, number of publications, number of citations, and years of active research were extracted using Scopus. RESULTS: The academic ranks of 237 faculty members were used for analysis; of this group, 16.95% of associate professors were female. Women were less frequently represented in higher academic ranks, and women were also less frequently represented in leadership ranks (13.6% female vs 86.4% male). The h-index was comparable across genders. CONCLUSION: Female nuclear medicine specialists are underrepresented in academic and leadership positions compared with their male counterparts. This difference in numbers is unlikely to be because of academic performance given that both genders had comparable academic performance metrics in our study. The results show the need for devising strategies to promote diversity in academic and leadership positions across nuclear medicine specialists.

Characterization of Hydrocarbon-Degrading Bacteria in Constructed Wetland Microcosms Used to Treat Crude Oil Polluted Water.

Ten plant species were grown in constructed wetlands (CWs) to remediate water containing 2% (w/v) crude oil. The plant species with better growth and biomass production were Typha latifolia and Cyperus laevigatus, and they were significantly correlated (R2 = 0.91) with hydrocarbon degradation. From T. latifolia and C. laevigatus, 33 hydrocarbon-degrading bacterial strains were isolated from the rhizosphere, and root and shoot interiors. More diversified bacteria were found in the rhizosphere and endosphere of C. laevigatus than those of T. latifolia. The predominant cultural hydrocarbon-degrading bacteria were shown to belong to the genera Pseudomonas, Acinetobacter and Bacillus. In addition to genes involved in hydrocarbon degradation, most of the bacteria displayed multiple plant growth promoting (PGP) activities. This study suggests the importance of selecting suitable bacterial strains with hydrocarbon degradation and PGP activities for improving the efficacy of CWs used in remediating water contaminated with crude oil.

Effects of aqueous leaves extract of Holoptelea integrifolia (Roxb) Planch on liver and kidney histopathology of albino rats.

Histopathological studies are an essential element to ascertain comprehensive safety profile of a drug. Unfortunately limited data are available about the toxicity of herbal remedies. Since a popular medicinal plant Holoptelea integrifolia (Roxb) Planch. contains various bioactive molecules, the present study is aimed to assess the histopathological alterations induced by aqueous extract of Holoptelea integrifolia on liver and kidney of wistar albino rat. In this study 60 rats divided in two groups; control and treated with aqueous extract of Holoptelea integrifolia (250mg/kg body weight) for 5 days. Histopathlogical studies by hematoxylin and eosin (H&E) staining were done on the liver and kidney tissues at the end of dosing by using standard procedure. Microscopic examination was then carried out to observe any pathological changes in the animals. The result showed that there is no significant variation in the basic architecture of liver and kidney as compared to control male wistar albino rats. In conclusion, aqueous extract of leaves of H. integrifolia may be safe and nontoxic. Further work on pharmacological aspects is required to evaluate the clinical potential of this plant for different ailments.